title: A stewardship program's retrospective evaluation of vancomycin AUC24/MIC and time to microbiological clearance in patients with methicillin-resistant Staphylococcus aureus bacteremia and osteomyelitis.
abstract: BACKGROUND
  Current guidelines for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia recommend targeting a vancomycin AUC24/MIC ≥400. Data on the association between AUC24/MIC and microbiological clearance in patients with concomitant MRSA bacteremia and MRSA osteomyelitis are limited.
  
  
  OBJECTIVE
  The objective of this study is to evaluate the association between the vancomycin AUC24/MIC and time to microbiological clearance in patients with concomitant MRSA bacteremia and MRSA osteomyelitis.
  
  
  METHODS
  Adult inpatients with concomitant MRSA bacteremia and MRSA osteomyelitis treated with vancomycin from January 1, 2007, through December 31, 2011, were evaluated. Classification and regression tree analysis was used to identify the AUC24/MIC associated with time to microbiological clearance.
  
  
  RESULTS
  Fifty-nine patients had complete data available for review and were included in the analysis. Classification and regression tree analysis identified an AUC/MIC of 293 as the breakpoint that provides the greatest difference in time to microbiological clearance. On univariate analysis, mean (SD) time to clearance was 2 days shorter when the AUC/MIC was >293 (4 [2] days vs 6 [3] days, P = 0.01). Mean (SD) infection-related length of stay was 13 (6) versus 18 (14) days in patients with an AUC24/MIC ratio >293 or ≤293, respectively (P = 0.25). In patients with an AUC24/MIC ≤293, 39% versus 17% (P = 0.09) had recurrent bacteremia and were readmitted compared with patients with an AUC/MIC >293. Only 9% were able to achieve an AUC24/MIC >293 when the vancomycin MIC was >1 μg/mL.
  
  
  CONCLUSIONS
  We observed a >2.5-fold increase in time to microbiological clearance in patients with concomitant MRSA bacteremia and MRSA osteomyelitis unable to achieve a vancomycin AUC24/MIC >293. A 5-day increase in hospital and infection-related length of stay was observed when this target was not achieved. Recurrence of bacteremia and hospital readmissions were higher in the cohort who did not achieve an AUC24/MIC >293. Only 9% of patients were able to achieve an AUC24/MIC >293 if the isolate MIC was >1 μg/mL. Trough concentration did not correlate with AUC24/MIC. In patients with concomitant MRSA bacteremia and MRSA osteomyelitis treated with vancomycin, stewardship programs should optimize pharmacodynamic parameters, specifically AUC24/MIC, or alternative therapies should be considered.
authors.affiliation: Department of Pharmacy, Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Gawronski
authors.forename: Debra A
authors.initials: DA
authors.lastname: Goff
authors.forename: Jack
authors.initials: J
authors.lastname: Brown
authors.forename: Tina M
authors.initials: TM
authors.lastname: Khadem
authors.forename: Karri A
authors.initials: KA
authors.lastname: Bauer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology; D015397:Program Evaluation; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D014640:Vancomycin / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin